Ray Wang, PhD

Department of Biochemistry & Biophysics
University of California, San Francisco
600 16th St., Room S414
San Francisco CA
(415) 476-9375 (Ph)


My research goal is to uncover the molecular principles of how Hsp90/Hsp70 chaperone machinery regulates the activity of the glucocorticoid receptor (GR). With a joint effort with Chari Noddings, we are using a hybrid approach combining cryo-EM and Rosetta structural modeling tools to determine atomic structures of GR-bound chaperone machinery in two critical states on the chaperone-assisted protein maturation pathway –– the client-loading and client-maturation complexes. Furthermore, we are applying a combination of in vitro biochemical and biophysical approaches to elucidate how Hsp90’s two events of ATP hydrolysis are coupled to GR’s conformational remodeling and to the assembly/disassembly of the Hsp90/Hsp70 chaperone machinery. It's been extremely fun with quite a lot of surprises and excitement so far. 



( * denotes equal contribution)

17. Wang RY-R, Noddings CN, Kirschke E, Agard DA. The molecular mechanism of chaperone-regulated GR function revealed by cryo-EM. [In preparation]

16. Leman JK*, Weitzner BD*, Lewis SM*, (Developers from RosettaCommons; Wang RY-R), Bonneau R.  Macromolecular modeling and design in Rosetta: new methods and frameworks. Nature Methods (2020). [Under revision]

15. Kalia R, Wang RY-R, Yusuf Ali, Thomas PV, Agard DA, Shaw JM, Frost A. Structural basis of mitochondrial receptor binding and GTP driven conformational constriction by dynamin-related Protein 1. Nature (2018) 558:401-405.

14. Wang RY-R, Song Y, Barad BA, Cheng Y, Fraser JS, DiMaio F. Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta. eLife (2016) pii: e17219.

13. Verba KA, Wang RY-R, Arakawa A, Liu Y, Shirouzu M, Yokoyama S, Agard DA. Atomic structure of Hsp90:Cdc37:Cdk4 reveals Hsp90 regulates kinase via dramatic unfolding. Science (2016) 352(6293):1542-7. 

12. Ovchinnikov S*, Park H*, Kim DE, Liu Y, Wang RY-R, Baker D. Structure prediction using sparse simulated NOE restraints with Rosetta in CASP11. Proteins (2016) 84 Suppl 1:181-8.

11. Ovchinnikov S*, Kim DE*, Wang RY-R, Liu Y, DiMaio F, Baker D. Improved de novo structure prediction in CASP11 by incorporating co-evolution information into Rosetta. Proteins (2016) 84 Suppl 1:67-75. 

10. Barad BA, Echols N, Wang RY-R, Cheng Y, DiMaio F, Adams PD, Fraser JS. Side-chain-directed model and map validation for 3D electron cryo-microscopy. Nature Methods (2015) 12(10):943-6.

9. Blok N*, Tan D*, Wang RY-R*, Penczek P, Baker D, DiMaio F, Rapoport T, Walz T. An unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy. Proc Natl Acad Sci U S A. (2015) 112(30):E4017-E4025. [*Co-first authors]

8. Wang RY-R, Kudryashev M, Li X, Egelman EH, Basler M, Cheng Y, Baker D, DiMaio F. De novo protein structure determination from near-atomic resolution cryo-EM maps. Nature Methods (2015) 12(4):335-338.

7. Kudryashev M, Wang RY-R, Brackmann M, Scherer S, Maier T, Baker D, DiMaio F, Stahlberg H, Egelman EH, Basler M. The structure of the type six secretion system contractile sheath solved by cryo-electron microscopy. Cell (2015) 160(5):952-962.

6. Kufareva I, Katritch V, (Participants of GPCR Dock 2013; Wang RY-R), Stevens RC, Abagyan R. Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: Meeting new challenges. Structure (2014) 22(8):1120-1139. [Served as the leader and the main predictor of the Baker group, which was among the best performers in GPCR structure modeling]

5. Kim DE*, DiMaio F*, Wang RY-R, Song Y, Baker D. One contact for every twelve residues allows robust and accurate topology-level protein structure modeling. Proteins (2014) 82 Suppl 2:208-218.

4. Song Y*, DiMaio F*, Wang RY-R, Kim D, Miles C, Brunette T, Thompson J, Baker D. High-resolution comparative modeling with RosettaCM. Structure (2013) 21(10):1735-1742.

3. Wang RY-R, Han Y, Krassovsky K, Sheffler W, Tyka M, Baker D. Modeling disordered regions in proteins using Rosetta. PLoS One (2011) 6(7):e22060.

2. Huang W-L, Wang Y-R, Ko T-P, Chia C-Y, Huang K-F, Wang AH-J. Crystal structure and functional analysis of the glutaminyl cyclase from Xanthomonas campestris. Journal of Molecular Biology (2010) 401(3):374-388. [Cover story]

1. Huang K-F, Wang Y-R, Chang E-C, Chou T-L, Wang AH-J. A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl cyclases is critical for catalysis. The Biochemical Journal (2008) 411(1):181-190.